Transdermal administration of a drug can avoid first-pass metabolism of the drug in the liver and various side effects, and enables long-term administration of the drug in a sustained manner. Particularly, a patch preparation containing a drug in an adhesive layer has been actively developed, since an administration method thereof is easy and the dose can be controlled strictly.
As a method for efficient absorption of a drug from a patch preparation into the body through the skin, a method of increasing the concentration of a drug in an adhesive layer, and a method of increasing the area and thickness of an adhesive layer are known. However, as the concentration of a drug contained in an adhesive layer increases, crystals of the drug tend to be formed in the adhesive layer, and when the area and thickness of the adhesive layer of a patch preparation are increased, problems occur such as lower handling property when the patch preparation is used, increased unpleasant feeling during adhesion to the skin.
When a small amount of crystal of the drug is precipitated in an adhesive layer, an adverse influence is not exerted on the usefulness of a patch preparation; however, it may give rise to a concern of the patients about degradation of the quality, and may induce inconveniences such as hesitation in using the patch preparation and the like. When a large amount of crystal of the drug is precipitated, releasability of the drug changes, and when the surface of an adhesive layer is covered with the crystal, the area having adhesiveness decreases, and therefore, adhesiveness to the skin decreases, and the patch preparation may not stand long-term adhesion.
JP-A-2006-513195 and JP-B-3566301 disclose a heat treatment of an adhesive layer containing a drug at a supersaturation concentration to manufacture a patch preparation suppressed in crystallization. However, since the temperature of the heating step in the manufacturing method is not less than the melting point of the drug, denaturation of the drug is feared. Moreover, in the method described in said patent, a laminate sheet with a laminate constitution of support/drug-containing adhesive layer/release liner is cut into a patch preparation with a given shape. According to this method, since the laminate sheet after cutting out the patch preparation is generally discarded as a waste, manufacturing loss is involved. Moreover, since the laminate sheet including the manufacturing loss is manufactured, unnecessary material costs are also involved.